Long-term exposure to ambient fine particulate components and leukocyte epigenome-wide DNA Methylation in older men: the Normative Aging Study

Cuicui Wang*, Heresh Amini, Zongli Xu, Adjani A. Peralta, Mahdieh Danesh Yazdi, Xinye Qiu, Yaguang Wei, Allan Just, Jonathan Heiss, Lifang Hou, Yinan Zheng, Brent A. Coull, Anna Kosheleva, Andrea A. Baccarelli, Joel D. Schwartz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Epigenome-wide association studies of ambient fine particulate matter (PM2.5) have been reported. However, few have examined PM2.5 components (PMCs) and sources or included repeated measures. The lack of high-resolution exposure measurements is the key limitation. We hypothesized that significant changes in DNA methylation might vary by PMCs and the sources. Methods: We predicted the annual average of 14 PMCs using novel high-resolution exposure models across the contiguous U.S., between 2000–2018. The resolution was 50 m × 50 m in the Greater Boston Area. We also identified PM2.5 sources using positive matrix factorization. We repeatedly collected blood samples and measured leukocyte DNAm with the Illumina HumanMethylation450K BeadChip in the Normative Aging Study. We then used median regression with subject-specific intercepts to estimate the associations between long-term (one-year) exposure to PMCs / PM2.5 sources and DNA methylation at individual cytosine-phosphate-guanine CpG sites. Significant probes were identified by the number of independent degrees of freedom approach, using the number of principal components explaining > 95% of the variation of the DNA methylation data. We also performed regional and pathway analyses to identify significant regions and pathways. Results: We included 669 men with 1,178 visits between 2000–2013. The subjects had a mean age of 75 years. The identified probes, regions, and pathways varied by PMCs and their sources. For example, iron was associated with 6 probes and 6 regions, whereas nitrate was associated with 15 probes and 3 regions. The identified pathways from biomass burning, coal burning, and heavy fuel oil combustion sources were associated with cancer, inflammation, and cardiovascular diseases, whereas there were no pathways associated with all traffic. Conclusions: Our findings showed that the effects of PM2.5 on DNAm varied by its PMCs and sources.

Original languageEnglish (US)
Article number54
JournalEnvironmental Health: A Global Access Science Source
Issue number1
StatePublished - Dec 2023


  • DNA methylation
  • Epigenome-wide association study
  • PM components
  • Pathway analyses
  • Sources

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis


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